Exp Physiol 95.10 pp 1033–1042 1033 Experimental Physiology – Research Paper The effect of cooling on the contractility of equine digital small lamellar arteries: modulating role of the endothelium Hector Zerpa 1 , Yoel Berhane 1 , Jonathan Elliott 1 and Simon R. Bailey 2 1 Department of Veterinary Basic Sciences, Royal Veterinary College, University of London, Royal College Street, London NW1 0TU, UK 2 Faculty of Veterinary Science, University of Melbourne, Parkville, Victoria 3010, Australia The equine hoof displays thermoregulatory functions, and the blood vessels lying under the hoof wall are temperature sensitive. The aim of this study was to investigate the effect of cooling on the contractile responses to α-adrenoceptor and 5-HT receptor stimulation in equine small lamellar arteries using wire myography. The role of the endothelium in the response mediated by 5-HT was also evaluated. Moderate cooling caused a reduction of the contraction induced by depolarizing Krebs solution (DKS, containing 118 mm KCl) and the maximal contraction caused by UK-14304 (α 2 -adrenoceptor agonist). The potency of methoxamine (α 1 -adrenoceptor agonist) was reduced by cooling [pD 2 (−log EC 50 ) at 22 ◦ C, 5.7 (5.5–6.0) versus 30 ◦ C, 5.9 (5.7– 6.1)]; however, the efficacy was maintained. The contractions evoked by sumatripan and α- methyl 5-HT (5-HT receptor agonists) were not modified by moderate cooling. In contrast, a cooling-enhanced contraction was observed in response to 5-HT [maximum response (E max ) at 22 ◦ C, 213.2 ± 13% DKS versus 30 ◦ C, 179.9 ± 11% DKS]. Furthermore, this effect was more evident in endothelium-denuded lamellar arteries (E max at 22 ◦ C, 270.2 ± 26% DKS versus 30 ◦ C, 172.2 ± 20% DKS), suggesting a potential modulating role of the endothelium. The l-NAME/ibuprofen-resistant relaxation in response to carbachol was reduced by cooling in small lamellar arteries precontracted with 5-HT but not phenylephrine. Therefore, a moderate reduction of temperature modulates the reactivity of small lamellar arteries by enhancing the 5-HT-mediated contraction, but inhibits the α-adrenoceptor-mediated response. Furthermore, the endothelium of these blood vessels may play an important role in preventing excessive vasoconstriction in response to 5-HT and maintaining digital blood flow in cool environmental temperatures. (Received 19 April 2010; accepted after revision 16 July 2010; first published online 21 July 2010) Corresponding author S. R. Bailey: Faculty of Veterinary Science, University of Melbourne, Parkville, Victoria 3010, Australia. Email: bais@unimelb.edu.au Highly vascular dermal tissues in ungulates, such as horns and hooves, have been proposed to accomplish a thermoregulatory role (Pollitt, 1992; Picard et al . 1999). Cooling-enhanced vascular reactivity has been found in large and small blood vessels, including veins and arteries (Flavahan et al . 1985; Chotani et al . 2000). Lemons et al . (1987) proposed a model whereby heat transfer can occur from arteries of 50 to 1000 μm internal diameter, as well as capillaries. The classification of resistance vessels according to size is unclear; Christensen & Mulvany (2001) suggested that the evidence that arteries having a diameter of 100–300 μm are true resistance vessels is mostly circumstantial, and varies according to the species and the vascular bed (Mulvany & Aalkjaer, 1990). Therefore, it is still unclear whether the cooling-enhanced vasoconstriction reported in large equine digital veins obtained from the coronet band above the hoof (Zerpa et al . 2007) is also manifested in resistance vessels, in particular those obtained from the lamellar tissue inside the hoof capsule. In addition to a thermoregulatory role, cooling- enhanced vasoconstriction in the digits may have pathophysiological implications. For example, Raynaud’s phenomenon in humans is a condition characterized by cooling-induced vasoconstriction and digital ischaemia (Flavahan, 2008). Raynaud’s phenomenon has been compared with the crippling equine digital disease, laminitis (Hood et al . 1990). Equine laminitis is a condition where the laminar structures supporting the third phalanx within the hoof capsule break down, which C  2010 The Authors. Journal compilation C  2010 The Physiological Society DOI: 10.1113/expphysiol.2010.053686